He served as the chairman of the "Yes" side during the 1980 referendum on Quebec sovereignty. In 1988 he was appointed ambassador to France, then joined Brian Mulroney's cabinet as secretary of state and later minister of the environment (1988-1990). In 1990 he resigned and formed the Bloc Québécois, serving as Leader of the Opposition, 1993-1996. He resigned in 1996 to become the leader of the Parti Québécois and premier of Quebec. He retired from politics in 2001.
He lost a leg to necrotizing fasciitis ("flesh-eating disease"), becoming possibly the most famous victim of this rare disease.
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